This invention relates to the purification of fluorocarbon compounds to remove hydrogen-containing materials and/or to render the fluorocarbons less toxic to living organisms.
Biological applications of fluorocarbon compounds have expanded in recent years, therefore requiring careful attention to purification of the compounds to provide pharmaceutical grade material. Typical of such applications are the blood substitute and perfusion media uses of perfluorinated cyclic hydrocarbons described in U.S. Pat. Nos. 3,911,138--Clark and 4,105,798 --Moore and Clark. The latter patent describes the purification of a perfluoro polycyclic hydrocarbon mixture by refluxing with 10% aqueous potassium hydroxide (KOH). It is also known that fluorocarbons may be purified prior to biological evaluations by refluxing with 4N aqueous KOH for several hours to remove partially fluorinated, hydrogen-containing by-products.
However, even with several treatments with fairly concentrated KOH solutions (about 30 wt.%), the known treatments have reduced the hydrogen content only about 30-50%, e.g., in one type of fluorocarbon from about 1000 ppm in the starting material to about 500-700 ppm in the product, and in another type from about 100 ppm in the starting material to about 50 ppm in the product. (In this specification, ppm of hydrogen means the weight of hydrogen atoms relative to the total weight of the fluorocarbon compounds determined by infrared spectroscopy.) Since it is now generally believed that for biological applications, especially for treatment of human medical conditions, the hydrogen content of the fluorocarbons should be less than about 25 ppm, preferably less than about 5 ppm, it is apparent that the conventional KOH purification procedure is inadequate, even though the conventional procedure, when measured by some toxicity test procedures, appears to substantially reduce or even eliminate toxicity in the purified product. The reason for this inadequacy is that substantial testing of perfluorocarbons in humans has not yet occurred. Therefore and also because toxicity is actually a function of both the nature of the species which contains hydrogen, as well as the hydrogen content, it is not known for sure what level of these hydrogen containing species can be regarded as non-toxic. Also, it is not known for sure whether hydrogen-containing species are toxic or, if not toxic, whether it reacts in the body to form something which is toxic. In view of the lack of knowledge about human toxicity, and the tremendous risks associated with erroneous judgments in respect thereof, the best solution is simply to remove as much of the hydrogen as possible and then evaluate the product on the basis of the amount of any residual hydrogen present and on toxicity tests of the product. In this regard the present process is much more effective in producing a less toxic product than the existing process.
"Purification" or similar term as used in this specification means elimination or substantial reduction of (1) acute toxicity as determined by in vitro tests such as the L-cell test or in vivo LD.sub.50 test, and/or (2) hydrogen content.
In U.S. Pat. No. 3,696,156--Weeks, KOH or other base, deposited on an alumina carrier, is disclosed for treatment of lower molecular weight fluoroperhalocarbons, containing two to six carbon atoms. This patent discloses treating saturated fluoroperhalocarbons with an agent prepared by dissolving alkali metal hydroxide in just sufficient amount of water to wet the surface of alumina, driving off gross water by gentle heating and then heating from about 250.degree. C. to about 400.degree. C. in a stream of nitrogen. The purpose of the treatment is to remove toxic unsaturated impurities such as octafluorobutenes, so that the fluoroperhalocarbon product will be sufficiently non-toxic for use as an aerosol propellant. There is no disclosure that the treating agent would be effective to solve the toxicity problems connected with hydrogen-containing compounds contained as impurities in higher molecular weight fluorocarbons which are useful as blood substitutes.